Genetic variations associated with tumors

Abstract

Nucleotide and amino acid variations associated with tumors are provided. Methods for detecting variations and for diagnosing and treating tumors are provided.

What is claimed is: 
     
       1. A method for predicting whether a tumor will respond to a therapeutic agent that targets a protein in the PI3K pathway, the method comprising
 (i) obtaining a test sample from a subject, wherein said test sample is from a tumor; 
 (ii) assaying the test sample for the presence of a nucleotide base substitution in a coding sequence of a PIK3R1 polynucleotide that results in an amino acid substitution at 564N in the SH2 domain of a PIK3R1 polypeptide, wherein the amino acid substitution results in activation of a PIK3CA polypeptide, and wherein the assay is performed by (a) contacting nucleic acid from the test sample with an allele-specific oligonucleotide that is specific for the nucleotide base substitution that results in an amino acid substitution at 564N in the SH2 domain of a PIK3R1 polypeptide under conditions suitable for hybridization of the allele-specific oligonucleotide to the nucleic acid; and (b) detecting the absence or presence of the allele-specific hybridization to detect the presence of the PIK3R1 substitution at amino acid 564N. 
 
     
     
       2. The method of  claim 1 , wherein the tumor is a solid tumor. 
     
     
       3. The method of  claim 1 , wherein the tumor is a colon tumor. 
     
     
       4. The method of  claim 1 , wherein the nucleotide base substitution is at 1732A corresponding to nucleotide 1732 of the cDNA sequence (SEQ ID NO:54) of the PIK3R1 gene. 
     
     
       5. The method of  claim 1 , wherein the amino acid substitution is 564N>D. 
     
     
       6. The method of  claim 1 , wherein the therapeutic agent targets a PIK3CA polypeptide. 
     
     
       7. The method of  claim 1 , further comprising administering to a human subject having the tumor an effective amount of a pharmaceutical formulation comprising an antagonist of PI3K signaling. 
     
     
       8. The method of  claim 7 , wherein the antagonist is an antagonist of a PIK3CA polypeptide. 
     
     
       9. The method of  claim 1 , wherein the assay is selected from a primer extension assay; an allele-specific primer extension assay; an allele-specific nucleotide incorporation assay; an allele-specific oligonucleotide hybridization assay; a 5′ nuclease assay; an assay employing molecular beacons; and an oligonucleotide ligation assay.